Rodman During this past grant year we have applied our stochastic estimation procedure to the problem of modeling the cellular kinetics of the antiviral nucleoside analogs PMEA and PMPA. The experimental data from this study involved intracellular measurements of these phosphonate analogs and their mono- and diphosphate derivatives, obtained following systemic administration of the parent compounds in monkeys. Our estimation approach allowed us to decouple the (complicated) systemic disposition processes from the cellular events. This was accomplished by using the measured plasma data, together with information on its error variance structure, as the uncertain input to the cellular metabolic process occurring in lymphoid and red blood cells. The model developed for the metabolism of PMPA and PMEA in lymphoid has help to clarify several of the contradictory reports on the metabolism of these compounds observed in vitro.